Shinji Fujihara

Biomechanical and biochemical characteristics of the mandibular condylar cartilage

The human masticatory system consists of a mandible which is able to move with respect to the skull at its bilateral temporomandibular joint (TMJ) through contractions of the masticatory muscles. Like other synovial joints, the TMJ is loaded mechanically during function. The articular surface of the mandibular condyle is covered with cartilage that is composed mainly of collagen fibers and proteoglycans. This construction results in a viscoelastic response to loading and enables the cartilage to play an important role as a stress absorber during function. To understand its mechanical functions properly, and to assess its limitations, detailed information about the viscoelastic behavior of the mandibular condylar cartilage is required. The purpose of this paper is to review the fundamental concepts of the biomechanical behavior of the mandibular condylar cartilage. This review consists of four parts. Part 1 is a brief introduction of the structure and function of the mandibular condylar cartilage. In Part 2, the biochemical composition of the mandibular condylar cartilage is summarized. Part 3 explores the biomechanical properties of the mandibular condylar cartilage. Finally, Part 4 relates this behavior to the breakdown mechanism of the mandibular condylar cartilage which is associated with the progression of osteoarthritis in the TMJ.

Function and Regulation of Osteopontin in Response to Mechanical Stress

Extensive histological study revealed the impairment of bone remodeling caused by mechanical stress in OPN knockout mice in a tooth movement system. Analysis of OPN promoter transgenic mice showed the mechanical stress response element(s) in the 5.5‐kb upstream region. These results were also obtained with the primary cultured cells.

PERIOSTIN regulates MMP-2 expression via the αvβ3 integrin/ERK pathway in human periodontal ligament cells

OBJECTIVE During orthodontic tooth movement, activation of the vascular system in the compressed periodontal ligament (PDL), which becomes hypoxic, is essential for periodontal tissue remodelling. PERIOSTIN, an extracellular matrix protein, is expressed in PDL and its concentration is increased on the compressive side during orthodontic tooth movement. PERIOSTIN promotes angiogenesis through upregulation of matrix metalloproteinase (MMP)-2, which has been shown to be expressed via αvβ3 integrin/extracellular signal-related kinase (ERK) signalling pathway and vascular endothelial growth factor (VEGF). Therefore, we hypothesized that hypoxia-induced PERIOSTIN promotes MMP-2 expression via αvβ3 integrin/ERK signalling and VEGF in PDL cells. METHODS Human PDL cells were cultured in condition medium containing desferrioxamine (DFO) to mimic hypoxia. The total RNA, cell lysates or supernatant were collected, and MMP2 and VEGF expression, PERIOSTIN expression and ERK phosphorylation, and MMP-2 activity were analysed by real-time RT-PCR, western blot analysis, and zymography, respectively. A recombinant human PERIOSTIN or PERIOSTIN siRNA was applied to the cells, then the total RNA was extracted to measure MMP-2 and VEGF expression. The cells were treated with αvβ3 integrin-blocking antibody or ERK inhibitor followed by PERIOSTIN stimulation. MMP-2 expression was measured by real-time RT-PCR. RESULTS PERIOSTIN was upregulated in a time-dependent manner in human PDL cells treated with DFO, a chemical hypoxia mimic. MMP-2 and VEGF expression, and MMP-2 activity were increased by DFO or PERIOSTIN treatment, and decreased by PERIOSTIN silencing. PERIOSTIN treatment also induced ERK phosphorylation, and PERIOSTIN-induced MMP-2 was reduced by αvβ3 integrin-blocking antibody or ERK inhibitor. CONCLUSION These data suggest that PERIOSTIN upregulates MMP-2 expression via the αvβ3 integrin/ERK signalling pathway and VEGF expression in human PDL cells.

Identification of Promoter Regions Involved in Cell- and Developmental Stage-Specific Osteopontin Expression in Bone, Kidney, Placenta, and Mammary Gland: An Analysis of Transgenic Mice†

Cell‐specific expression of GFP under the control of different lengths of the osteopontin promoter in transgenic mice identified the positive and negative regulatory regions for respective cell types. The results provide new insights for physiological and pathological expression of the osteopontin gene.

Analysis of gene expression profiles in human periodontal ligament cells under hypoxia: The protective effect of CC chemokine ligand 2 to oxygen shortage

Periodontal ligament (PDL) cells appear to play important functional roles in response to mechanical stress. We hypothesized that hypoxia caused by a deformation of blood vessels and the following ischaemia may play a crucial role in differential gene expression in PDL cells affected by mechanical stress. Gene induction in cultured human PDL cells by hypoxia was analyzed using cDNA array, followed by RT-PCR analysis. Eleven hypoxia-responsive genes were found differentially expressed under low-oxygen conditions in PDL cells. Among them, CCR2, CC chemokine ligand 2 (CCL2) receptor was studied in more detail since little information is available on the role of chemokines in adaptive responses of PDL cells under hypoxia. Here we investigate whether CCR2 mediates the signalling to maintain the homeostasis of PDL cells. We found that cell death of PDL cells was induced under hypoxia with down-regulation of CCL2 mRNA expression. However, the exogenous CCL2 prevented PDL cell death under oxygen shortage with the increment of cellular inhibitor of apoptosis (cIAP) mRNA expression. The present study demonstrated substantial effects of hypoxia on gene expression of CCL2 and CCR2 in PDL cells, indicating that mechanical loading accompanied with mild hypoxia allows PDL cells to elicit adaptive responses with up-regulation of CCR2.

Severity of alveolar cleft before palatoplasty affects vertical maxillofacial growth in 6-year-old patients with complete unilateral cleft lip and palate.

INTRODUCTION In this study, we investigated the association between the severity of alveolar clefts in infants and the succeeding maxillofacial growth in patients affected by complete unilateral cleft lip and palate. METHODS The subjects were 35 nonsyndromic patients affected by unilateral cleft lip and palate (n = 27) or bilateral cleft lip and palate (n = 8). Plaster models and lateral cephalograms taken at 6 years of age were analyzed and compared with the Japanese norms. In the unilateral cleft lip and palate patients, the relationship between the width of the alveolar cleft before palatoplasty and the skeletal characteristics was also explored. RESULTS Significant deficiencies of the posterior maxilla and steep palatal planes were noted in both the unilateral and bilateral cleft lip and palate patients. However, they were not clearly observed in the unilateral cleft lip and palate patients born with a small alveolar cleft and were correlated with the severity of alveolar cleft in infancy. Neither cleft type nor the severity of the alveolar cleft was implicated in the maxillary arch form in childhood, but the growth of the alveolar height on the cleft side was less in the unilateral cleft lip and palate patients born with a large alveolar cleft. CONCLUSIONS The severity of the alveolar cleft before palatoplasty affects the succeeding vertical maxillofacial growth in patients affected by unilateral cleft lip and palate; this suggests the necessity of a different diagnosis and treatment in unilateral cleft lip and palate patients according to the severity of the alveolar cleft in infancy.